Abstract
Dexamethasone suppression tests (DST) are practical, cheap and safe tests which are used to evaluate endogenous hypercortisolism. They are based on the principle that glucocorticoids exogenously given at supraphysiological doses suppress the production of CRH, ACTH and cortisol by binding to central glucocorticoid receptors. Lack of suppression of cortisol production suggest endogenous hypercortisolism. Additionally, DST may be used in the diagnosis of glucocorticoid remediable hyperaldosteronism. Due to strong glucocorticoid activity, lack of mineralocorticoid activity and lack of cross-reaction with the measurement of cortisol, dexamethasone is the preferred drug for the tests. As a screening tool in endogenous hypercortisolism, overnight 1 mg DST is used. If screening test is negative, hypercortisolism is excluded; but if the test is positive, 2-day 2 mg DST should be performed to confirm the diagnosis of Cushing’s syndrome. If endogenous hypercortisolism is confirmed, plasma ACTH should be measured. Undetectable plasma ACTH level suggest ACTH-independent Cushing’s syndrome, but inappropriately normal or high plasma ACTH level suggest ACTH-dependent Cushing’s syndrome. High dose DST (overnight 8 mg or 2-day 8 mg) should be performed to discriminate pituitary or extra-pituitary cause in the patients with ACTH-dependent Cushing’s syndrome. In the presence of pituitary Cushing’s disease, because of relatively preserved negative feedback mechanism, high dose dexamethasone may suppress ACTH. In ectopic ACTH secretion, due to lack of a normal negative feedback mechanism, ACTH cannot be suppressed by high dose dexamethasone. Extraordinarily, ectopic ACTH production in some neuroendocrine tumors may be suppressed by high dose dexamethasone, but no suppression may be observed in some patients with pituitary Cushing’s disease. When applying DST, serum and plasma samples should be collected in appropriate route, and they should be transferred by true collection tubes and in right storage conditions.
References
- 1. Liddle GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1960;20:1539-1560.
- 2. T.E.M.D. Adrenal ve Gonadal Hastalıklar Çalışma Grubu. Adrenal ve Gonadal Hastalıklar Kılavuzu. Türkiye Endokrinoloji ve Metabolizma Derneği, 2019.
- 3. Cronin C, Igoe D, Duffy MJ, Cunningham SK, McKenna TJ. The overnight dexamethasone test is a worthwhile screening procedure. Clin Endocrinol (Oxf). 1990;33:27-33.
- 4. Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F. Diagnosis and management of Cushing’s syndrome: Results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab. 1999;84(2):440-448.
- 5. Van Cauter E, Refetoff S. Evidence for two subtypes of Cushing’s disease based on the analysis of episodic cortisol secretion. N Engl J Med. 1985;312:1343-1349.
- 6. Montwill J, Igoe D, McKenna TJ. The overnight dexamethasone test is the procedure of choice in screening for Cushing’s syndrome. Steroids. 1994;59:296-298.
- 7. Zeiger MA, Thompson GB, Duh QY, The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocrine Practice. 2009;15:1-20.
- 8. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526-1540.
- 9. Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following lowdose dexamethasone administration. A new test to distinguish Cushing’s syndrome from pseudo-Cushing’s states. JAMA. 1993;269:2232-2238.
- 10. Isidori AM, Kaltsas GA, Mohammed S, Morris DG, Jenkins P, Chew SL, Monson JP, Besser GM, Grossman AB. Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 2003;88:5299-5306.
- 11. Aron DC, Raff H, Findling JW. Effectiveness versus efficacy: The limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1997;82:1780-1785.
- 12. Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ. Williams Textbook of Endocrinology. 14th edition, Philadelphia, Elsevier, 2020.
- 13. Tyrrell JB, Findling JW, Aron DC, Fitzgerald PA, Forsham PH. An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing’s syndrome. Ann Intern Med. 1986;104: 180-186.
- 14. Dichek HL, Nieman LK, Oldfield EH, Pass HI, Malley JD, Cutler GB Jr. A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1994;78:418-422.
- 15. Flack MR, Oldfield EH, Cutler GB Jr, Zweig MH, Malley JD, Chrousos GP, Loriaux DL, Nieman LK. Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome. Ann Intern Med. 1992;116:211-217.
- 16. Abou Samra AB, Dechaud H, Estour B, Chalendar D, Fevre- Montange M, Pugeat M, Tourniaire J. Beta-lipotropin and cortisol responses to an intravenous infusion dexamethasone suppression test in Cushing’s syndrome and obesity. J Clin Endocrinol Metab. 1985; 61: 116-119.
- 17. Atkinson AB, McAteer EJ, Hadden DR, Kennedy L, Sheridan B, Traub AI. A weight-related intravenous dexamethasone suppression test distinguishes obese controls from patients with Cushing’s syndrome. Acta Endocrinol (Copenh). 1989;120:753-759.
- 18. Workman RJ, Vaughn WK, Stone WJ. Dexamethasone suppression testing in chronic renal failure: Pharmacokinetics of dexamethasone and demonstration of a normal hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. 1986;63:741-746.
- 19. Ueland GÅ, Methlie P, Kellmann R, Bjørgaas M, Åsvold BO, Thorstensen K, Kelp O, Thordarson HB, Mellgren G, Løvås K, Husebye ES. Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test. Eur J Endocrinol. 2017;176:705-713.
- 20. Nickelsen T, Lissner W, Schöffling K. The dexamethasone suppression test and long-term contraceptive treatment: Measurement of ACTH or salivary cortisol does not improve the reliability of the test. Exp Clin Endocrinol. 1989;94:275- 280.
- 21. Qureshi AC, Bahri A, Breen LA, Barnes SC, Powrie JK, Thomas SM, Carroll PV. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol (Oxf). 2007;66:632-635.
- 22. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629-1638.
- 23. Kuzu F, Unal M, Gul S, Bayraktaroglu T. Pituitary apoplexy due to the diagnostic test in a Cushing’s disease patient. Turk Neurosurg. 2018;28:323-325.
- 24. Deksametazon. Kısa Ürün Bilgisi. (Accessed Date:30.01.2021, https://pdf.ilacprospektusu.com/1264-dekort-8mg-2ml-imiv- enjektabl-solusyon-iceren-ampul-kub.pdf)
- 25. Mayo Clinic Laboratories Test Catalog. (Accessed Date:30.01.2021 https://www.mayocliniclabs.com/testcatalog/ Overview/65484)
- 26. Mayo Clinic Laboratories.Test Catalog. (Accessed Date:30.01.2021 https://www.mayocliniclabs.com/testcatalog/ Overview/8411)
- 27. Yeo KJ, Babic N, Hannoush ZC, Weiss RE. Endocrine Testing Protocols: Hypothalamic Pituitary Adrenal Axis. (Accessed Date:30.01.2021,https://www.endotext.org/chapter/ endocrine-testing-protocols-hypothalamic-pituitary-adrenalaxis/)
Abstract
Deksametazon supresyon testleri (DST) endojen hiperkortizolizmin değerlendirilmesinde kullanılan pratik, ucuz ve güvenli testlerdir. Suprafizyolojik dozda ekzojen verilen sentetik glukokortikoidlerin, santral glukokortikoid reseptörlerine bağlanarak CRH, ACTH ve kortizol üretimini baskılaması ilkesine dayanır. Kortizol üretiminin baskılanmaması endojen hiperkortizolizmi düşündürür. Ayrıca DST, glukokortikoid yanıtlı hiperaldosteronizm tanısında da kullanılır. Güçlü glukokortikoid aktivitesinin olması, mineralokortikoid aktivitesinin olmaması ve kortizol ölçümlerine girmemesi sebebiyle deksametazon tercih edilir. Endojen hiperkortizolizm “tarama testi” olarak gecelik “1 mg DST” kullanılır. Tarama testi negatif çıkarsa (<1.8 mcg/dL) hiperkortizolizm dışlanır. Pozitif çıkarsa, yani kortizol düzeylerinde baskılanma olmazsa ≥1.8 mcg/dL) endojen hiperkortizolemiyi doğrulamak için “düşük doz deksametazon süpresyon testi” - 2 gün 2 mg DST- yapılır. Serum kortizol düzeylerinde baskılanma olmaz (≥1.8 mcg/dL) ve Cushin g Sendromu tanısı doğrulanırsa hiperkortizoleminin kaynağını saptamak için plazma ACTH ölçülür. Plazma ACTH ölçülemeyecek seviyedeyse ACTH bağımsız Cushing sendromu, plazma ACTH düzeyi uygunsuz olarak normal veya yüksek ise ACTH bağımlı Cushing sendromu düşünülür. ACTH bağımlı Cushing sendromu düşünülen hastalarda hipofizer veya hipofiz dışı bir patoloji ayırımı için yüksek doz DST (gecelik 8 mg veya 2 gün 8 mg) kullanılır. Hipofizer Cushing varlığında glukokortikoid negatif geri besleme kısmen korunduğundan yüksek doz deksametazon ile ACTH suprese olabilir. Ektopik ACTH salınımında ise glukokortikoid negatif geri besleme yanıtı kaybolduğundan yüksek doz deksametazon ile baskılanma olmaz. İstisna olarak, bazı nöroendokrin tümörlerdeki ektopik ACTH üretimi yüksek doz deksametazon ile baskılanabilirken, bazı hipofizer Cushing vakalarında baskılanma izlenmez. DST uygulanırken, sağlıklı sonuç alabilmek için, serum ve plazma örneklerinin uygun bir şekilde alındığından, doğru tüplerde ve saklama koşullarında taşındığından emin olunmalıdır.
References
- 1. Liddle GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1960;20:1539-1560.
- 2. T.E.M.D. Adrenal ve Gonadal Hastalıklar Çalışma Grubu. Adrenal ve Gonadal Hastalıklar Kılavuzu. Türkiye Endokrinoloji ve Metabolizma Derneği, 2019.
- 3. Cronin C, Igoe D, Duffy MJ, Cunningham SK, McKenna TJ. The overnight dexamethasone test is a worthwhile screening procedure. Clin Endocrinol (Oxf). 1990;33:27-33.
- 4. Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F. Diagnosis and management of Cushing’s syndrome: Results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab. 1999;84(2):440-448.
- 5. Van Cauter E, Refetoff S. Evidence for two subtypes of Cushing’s disease based on the analysis of episodic cortisol secretion. N Engl J Med. 1985;312:1343-1349.
- 6. Montwill J, Igoe D, McKenna TJ. The overnight dexamethasone test is the procedure of choice in screening for Cushing’s syndrome. Steroids. 1994;59:296-298.
- 7. Zeiger MA, Thompson GB, Duh QY, The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocrine Practice. 2009;15:1-20.
- 8. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526-1540.
- 9. Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following lowdose dexamethasone administration. A new test to distinguish Cushing’s syndrome from pseudo-Cushing’s states. JAMA. 1993;269:2232-2238.
- 10. Isidori AM, Kaltsas GA, Mohammed S, Morris DG, Jenkins P, Chew SL, Monson JP, Besser GM, Grossman AB. Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 2003;88:5299-5306.
- 11. Aron DC, Raff H, Findling JW. Effectiveness versus efficacy: The limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1997;82:1780-1785.
- 12. Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ. Williams Textbook of Endocrinology. 14th edition, Philadelphia, Elsevier, 2020.
- 13. Tyrrell JB, Findling JW, Aron DC, Fitzgerald PA, Forsham PH. An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing’s syndrome. Ann Intern Med. 1986;104: 180-186.
- 14. Dichek HL, Nieman LK, Oldfield EH, Pass HI, Malley JD, Cutler GB Jr. A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1994;78:418-422.
- 15. Flack MR, Oldfield EH, Cutler GB Jr, Zweig MH, Malley JD, Chrousos GP, Loriaux DL, Nieman LK. Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome. Ann Intern Med. 1992;116:211-217.
- 16. Abou Samra AB, Dechaud H, Estour B, Chalendar D, Fevre- Montange M, Pugeat M, Tourniaire J. Beta-lipotropin and cortisol responses to an intravenous infusion dexamethasone suppression test in Cushing’s syndrome and obesity. J Clin Endocrinol Metab. 1985; 61: 116-119.
- 17. Atkinson AB, McAteer EJ, Hadden DR, Kennedy L, Sheridan B, Traub AI. A weight-related intravenous dexamethasone suppression test distinguishes obese controls from patients with Cushing’s syndrome. Acta Endocrinol (Copenh). 1989;120:753-759.
- 18. Workman RJ, Vaughn WK, Stone WJ. Dexamethasone suppression testing in chronic renal failure: Pharmacokinetics of dexamethasone and demonstration of a normal hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. 1986;63:741-746.
- 19. Ueland GÅ, Methlie P, Kellmann R, Bjørgaas M, Åsvold BO, Thorstensen K, Kelp O, Thordarson HB, Mellgren G, Løvås K, Husebye ES. Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test. Eur J Endocrinol. 2017;176:705-713.
- 20. Nickelsen T, Lissner W, Schöffling K. The dexamethasone suppression test and long-term contraceptive treatment: Measurement of ACTH or salivary cortisol does not improve the reliability of the test. Exp Clin Endocrinol. 1989;94:275- 280.
- 21. Qureshi AC, Bahri A, Breen LA, Barnes SC, Powrie JK, Thomas SM, Carroll PV. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol (Oxf). 2007;66:632-635.
- 22. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629-1638.
- 23. Kuzu F, Unal M, Gul S, Bayraktaroglu T. Pituitary apoplexy due to the diagnostic test in a Cushing’s disease patient. Turk Neurosurg. 2018;28:323-325.
- 24. Deksametazon. Kısa Ürün Bilgisi. (Accessed Date:30.01.2021, https://pdf.ilacprospektusu.com/1264-dekort-8mg-2ml-imiv- enjektabl-solusyon-iceren-ampul-kub.pdf)
- 25. Mayo Clinic Laboratories Test Catalog. (Accessed Date:30.01.2021 https://www.mayocliniclabs.com/testcatalog/ Overview/65484)
- 26. Mayo Clinic Laboratories.Test Catalog. (Accessed Date:30.01.2021 https://www.mayocliniclabs.com/testcatalog/ Overview/8411)
- 27. Yeo KJ, Babic N, Hannoush ZC, Weiss RE. Endocrine Testing Protocols: Hypothalamic Pituitary Adrenal Axis. (Accessed Date:30.01.2021,https://www.endotext.org/chapter/ endocrine-testing-protocols-hypothalamic-pituitary-adrenalaxis/)
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Collection |
| Authors | |
| Publication Date | April 24, 2021 |
| Acceptance Date | March 23, 2021 |
| Published in Issue | Year 2021 Volume: 5 Issue: 1 |
